Liver Transplantation in Patients with Acute-onChronic Liver Failure: Challenging the Limits

Acute-on-chronic liver failure (ACLF) is one of the main causes of death on the waiting list. Liver transplantation (LT) is the only curative treatment for patients with ACLF and therefore it should be considered in all cases. However, the applicability of LT in patients with ACLF is challenging, given the scarcity of donors and the high short-term mortality of these patients. Organ allocation has traditionally been prioritised according to the model for end-stage liver disease (MELD) system. However, the accuracy of MELD score is limited in patients with ACLF. In this article, the authors review the outcomes of patients with ACLF before and after LT, highlighting its clinical course, the feasibility of LT in the sickest patients, the role of the organ allocation system, and possible indicators of futility.

Mitigating selection bias in organ allocation models

Background The lung allocation system in the U.S. prioritizes lung transplant candidates based on estimated pre- and post-transplant survival via the Lung Allocation Scores (LAS). However, these models do not account for selection bias, which results from individuals being removed from the waitlist due to receipt of transplant, as well as transplanted individuals necessarily having survived long enough to receive a transplant. Such selection biases lead to inaccurate predictions. Methods We used a weighted estimation strategy to account for selection bias in the pre- and post-transplant models used to calculate the LAS. We then created a modified LAS using these weights, and compared its performance to that of the existing LAS via time-dependent receiver operating characteristic (ROC) curves, calibration curves, and Bland-Altman plots. Results The modified LAS exhibited better discrimination and calibration than the existing LAS, and led to changes in patient prioritization. Conclusions Our approach to addressing selection bias is intuitive and can be applied to any organ allocation system that prioritizes patients based on estimated pre- and post-transplant survival. This work is especially relevant to current efforts to ensure more equitable distribution of organs.

Bioethics, Rent-Seeking, and Death: Examining the Opposition to Kidney Markets

The market for kidneys offers a case study of Baptists and Bootleggers. In almost every country, sales are currently illegal and donated organs are allocated by a central planner. Thousands of people die every year, because of the shortage caused by the absence of markets. This paper starts by examining the free-market alternative, and shows that a market would solve the shortage (and thus unnecessary deaths). It then uses gains-from-trade analysis to explain why current vested interests oppose a move to a market, despite the immense potential for saved lives. In a shift to a market, gains from trade would be distributed away from lucky patients (who receive a zero-price kidney) and various industries that benefit from the shortage (dialysis, medical equipment, etc.); these “Bootleggers” form an alliance with “Baptists” (altruistic donors, large segments of the bioethics community, and organ allocation central planners).

Vascularized composite allotransplantation

Vascularized composite allotransplants contain the products of multiple cell lineages to reconstruct the form and function of complex, composite tissue defects. This chapter discusses the ethical principles and the immunology behind composite transplantation, including the selection of immunomodulatory agents and the immune basis and treatment of rejection. The principles of organ allocation and candidate preparation are presented prior to discussion of the clinical applications and outcomes of hand, face, abdominal wall, uterus, penis, and lower limb transplantation.

Diminished autonomy and justice in liver transplantation – The price of scarcity?

Patient autonomy and distributive justice are fundamental ethical principles that may be at risk in liver transplant units where decisions are dictated by the need to maximise the utility of scarce donor organs. The processes of patient selection, organ allocation and prioritisation on the wait list have evolved in a constrained environment, leading to high levels of complexity and low transparency. Regarding paternalism, opaque listing and allocation criteria, patient factors such as passivity, guilt, chronic illness and sub-clinical encephalopathy are cited as factors that may inhibit patient engagement. Regarding justice, established regional, gender and race based inequities are described. The paradox whereby hepatologists both advocate for individual patients and discharge their duty of stewardship to apportion organs according to larger utilitarian principles is explored. Competing subjective factors such as physicians’ perception of moral responsibility, the qualitative nature of expert medical assessment and institutional or personal loyalty to re-transplantation candidates are described. Realistic limits of self-determination and justice are discussed, and possible future directions in terms of patient involvement proposed.

Do I Own My Organs?

This chapter evaluates the author's narrative after her meeting with Deb Porter Gill. It offers a variety of outcomes if the author had not liked Deb and withdrawn the offer to donate. That could have been for any reason, including political values, lifestyle, religion, or skin color. The chapter argues that living donors are treated by the law and by doctors as the owners of their bodies, and their body parts are considered goods that they can donate or not to whomever they want. The chapter examines the justice-based approach to organ allocation. In contrast with the living donors, cadaveric donors are generally put into national pools and allocated according to nationally agreed-upon criteria. The chapter states that their use is governed not by the autonomy-based preferences of the donor or the donor's family but, instead, by considerations of justice that are built into the administrative rules that dictate how organs should be allocated. Ultimately, the chapter presents the practical reasons for treating cadaveric organs differently than organs from a living donor.

Mortality and its Determinants in Adult Patients with End-stage Liver Disease on Waiting List for Liver Transplantation: A Preliminary Report on Baseline Data

Background: Prevention of death in patients on the waiting list for liver transplantation (LT) is a major concern to prioritize organ allocation. Since the model for the end-stage liver disease (MELD) and its modifications have many shortages, there is a need for further refinement of the allocation strategy. Objectives: The current study aimed at assessing the predictors of mortality in LT candidates in a more comprehensive manner with the possible implications to improve the care of such patients and assist in developing better strategies for organ allocation. Methods: In the current cohort study, 544 adult LT candidates with end-stage liver disease were followed up for a mean of 12 months in three-month intervals. Data analysis was performed in Nutritionist, SPSS, and R software, using Kaplan-Meier, Cox proportional hazard (HRC), and LASSO Cox regression hazard (HRL) tests. Results: The mean age of the patients was 46.7 ± 13.7 years; the majority were male (n = 336, 61.7%). At the end of the study, 414 (76.1%) subjects were still alive and 130 (23.9%) dead. The cumulative percentages of death were 33.1%, 57.7%, and 79.2% after 3, 6, and 12 months of waiting for a donor, respectively. Although there was a strong association between having hepatopulmonary syndrome (HPS) (HRC = 4.7, HRL = 1.8), a history of myocardial infarction (MI) (HRC = 3.3, HRL = 1.6), low-carbohydrate (CHO) diet (HRC = 2.7, HRL = 1.5), and mortality, it was weak for MELD score. Moreover, a serum level of CA 125, high polymorphonuclear (PMN) count, weight loss, a high level of alanine aminotransferase (ALT), positive hepatitis B virus (HBV) markers, high mean corpuscular volume (MCV) of red blood cells, ascites, and edema of gallbladder wall had association with mortality in LT patients. Conclusions: In addition to MELD score, HPS, a history of MI, low CHO intake, weight loss, ascites, PMN, CA 125, ALT, hepatitis B surface antigen, MCV, blood urea nitrogen, and gallbladder wall thickness are predictors of mortality in LT candidates and need to be considered in the LT allocation system.